Nonalcoholic fatty liver disease (Homo sapiens)

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1-4, 8-11CxIER StressInsulin ResistanceTGFB1UQCRQCYP2E1SDHBFatty Acid BiosynthesisselonsertibNDUFB1AKT1SDHDNDUFAB1COX8ANDUFC1NDUFB4TNFR1COX2PRKAG2NDUFA5EIF2S1NDUFA2NDUFB7NDUFB2NDUFA1JNK1ATF4RELAFASNDUFS4SDHANDUFB6NDUFA4NDUFV1PI3K-AKT SignalingNDUFA6NDUFS1COX4I1NDUFS8ITCHNDUFB10CASP7NR1H3NDUFA10MLXIPNDUFS7NDUFB11COX6CDDIT3Insulin SignalingEIF2AK3UQCRHLADIPOR1NDUFA12ApoptosisBBC3UQCRC2JUNfatty acidsD-glucoseNDUFB3JNK2RAC1NDUFS6UQCRFS1COX1NDUFA13NDUFC2-KCTD14ROSIL6RNDUFA8Oxidative PhosphorylationCOX3ADIPOR2SREBF1MLXIPLPKLRNDUFS5NDUFA11TRAF2COX7BSOCS3COX5BFASLGNDUFA4L2AKT3LEPNDUFV2mir21BIDINSMAP3K5NDUFB8CYC1NDUFB5CXCL8ADIPOQLEPRNDUFA3PIK3R2RXRATNFPRKAB2IRS1GSK3BUQCR11PPARANDUFV3UQCRBMLXFXRAKT2COX6B1TNF SignalingPIK3CDXBP1PIK3R3IL1AMAP3K11BAK1CYTBNDUFS3BAXCASP8COX8CIRS2CxICOX7A2LCOX4I2PRKAG1PRKAB1GSK3ANFKB1PRKAA2CYCSCOX7CCASP3COX6A1COX6B2PRKAG3IL6NDUFB9UQCR10PRKAA1COX7A2PIK3CBCOX7A1PIK3R1CDC42UQCRHCOX7B2NDUFC2IKBKBCOX5APPAR SignalingNDUFA7Lipogenic EnzymesCOX6A2oxysterolsERN1CEBPANDUFS2SDHCNDUFA9INSRPIK3CAIL1BTGF SignalingUQCRC157P6HepatocyteIL6CxIICxIIICxIVCxIICxIIICxIVIL1ATNFTNFFASLGGlucose UptakeFatty Acid OxidationDevelopment of NAFLDDevelopment of SteatoheptisisHepatocyte InjuryMitochondriadysfunctionIL1BBIMTCA CycleCCL2VCAM1NASHFibrogenesisSMAD7


Description

Nonalcoholic fatty liver disease (NAFLD) is a condition in which too much fat is stored in the liver. Nonalcoholic steatohepatitis (NASH) is a type of NAFLD marked by liver inflammation, which may progress to scarring and irreversible damage similar to that caused by heavy alcohol use. Components of glucose matabolism, insulin signaling, inflammation, oxidative stress, ER sgtress and apoptosis are all involved and interconnected in the progression of this disease.

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Bibliography

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  1. Larter CZ, Farrell GC; ''Insulin resistance, adiponectin, cytokines in NASH: Which is the best target to treat?''; J Hepatol, 2006 PubMed Europe PMC Scholia
  2. Seki E, Brenner DA, Karin M; ''A liver full of JNK: signaling in regulation of cell function and disease pathogenesis, and clinical approaches.''; Gastroenterology, 2012 PubMed Europe PMC Scholia
  3. Mantena SK, King AL, Andringa KK, Eccleston HB, Bailey SM; ''Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases.''; Free Radic Biol Med, 2008 PubMed Europe PMC Scholia
  4. Feldstein AE, Canbay A, Angulo P, Taniai M, Burgart LJ, Lindor KD, Gores GJ; ''Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis.''; Gastroenterology, 2003 PubMed Europe PMC Scholia
  5. Armstrong LE, Guo GL; ''Role of FXR in Liver Inflammation during Nonalcoholic Steatohepatitis.''; Curr Pharmacol Rep, 2017 PubMed Europe PMC Scholia
  6. Loomba R, Lawitz E, Mantry PS, Jayakumar S, Caldwell SH, Arnold H, Diehl AM, Djedjos CS, Han L, Myers RP, Subramanian GM, McHutchison JG, Goodman ZD, Afdhal NH, Charlton MR; ''Selonsertib (GS-4997), an ASK1 inhibitor, antagonizes multidrug resistance in ABCB1- and ABCG2-overexpressing cancer cells.''; Cancer Lett, 2018 PubMed Europe PMC Scholia
  7. Dattaroy D, Pourhoseini S, Das S, Alhasson F, Seth RK, Nagarkatti M, Michelotti GA, Diehl AM, Chatterjee S; ''Micro-RNA 21 inhibition of SMAD7 enhances fibrogenesis via leptin-mediated NADPH oxidase in experimental and human nonalcoholic steatohepatitis.''; Am J Physiol Gastrointest Liver Physiol, 2015 PubMed Europe PMC Scholia
  8. Malaguarnera M, Di Rosa M, Nicoletti F, Malaguarnera L; ''Molecular mechanisms involved in NAFLD progression.''; J Mol Med (Berl), 2009 PubMed Europe PMC Scholia
  9. Hotamisligil GS; ''Endoplasmic reticulum stress and the inflammatory basis of metabolic disease.''; Cell, 2010 PubMed Europe PMC Scholia
  10. Farrell GC, van Rooyen D, Gan L, Chitturi S; ''NASH is an Inflammatory Disorder: Pathogenic, Prognostic and Therapeutic Implications.''; Gut Liver, 2012 PubMed Europe PMC Scholia
  11. Malhi H, Kaufman RJ; ''Endoplasmic reticulum stress in liver disease.''; J Hepatol, 2011 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
123350view10:46, 17 July 2022EgonwMade multiple pathways clickable
98945view17:56, 16 October 2018AlexanderPicoOntology Term : 'liver disease pathway' added !
98944view17:55, 16 October 2018AlexanderPicoOntology Term : 'disease pathway' added !
98943view17:55, 16 October 2018AlexanderPicoOntology Term : 'nonalcoholic fatty liver disease' added !
98942view17:55, 16 October 2018AlexanderPicoOntology Term : 'hepatocyte' added !
98933view10:52, 16 October 2018EgonwReplaced a secondary ChEBI identifier.
98932view10:50, 16 October 2018EgonwRemoved funny chars in identifier.
98931view06:46, 16 October 2018AlexanderPicoModified description
98930view06:35, 16 October 2018AlexanderPicofixed paste characters in IDs
98929view06:31, 16 October 2018AlexanderPiconew pathway
98917view18:21, 15 October 2018AlexanderPicoNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ADIPOQGeneProduct9370 (Entrez Gene)
ADIPOR1GeneProduct51094 (Entrez Gene)
ADIPOR2GeneProduct79602 (Entrez Gene)
AKT1GeneProduct207 (Entrez Gene)
AKT2GeneProduct208 (Entrez Gene)
AKT3GeneProduct10000 (Entrez Gene)
ATF4GeneProduct468 (Entrez Gene)
ApoptosisPathwayWP254 (WikiPathways)
BAK1GeneProduct578 (Entrez Gene)
BAXGeneProduct581 (Entrez Gene)
BBC3GeneProduct27113 (Entrez Gene)
BIDGeneProduct637 (Entrez Gene)
BIMGeneProduct10018 (Entrez Gene)
CASP3GeneProduct836 (Entrez Gene)
CASP7GeneProduct840 (Entrez Gene)
CASP8GeneProduct841 (Entrez Gene)
CCL2GeneProduct6347 (Entrez Gene)
CDC42GeneProduct998 (Entrez Gene)
CEBPAGeneProduct1050 (Entrez Gene)
COX1GeneProduct4512 (Entrez Gene)
COX2GeneProduct4513 (Entrez Gene)
COX3GeneProduct4514 (Entrez Gene)
COX4I1GeneProduct1327 (Entrez Gene)
COX4I2GeneProduct84701 (Entrez Gene)
COX5AGeneProduct9377 (Entrez Gene)
COX5BGeneProduct1329 (Entrez Gene)
COX6A1GeneProduct1337 (Entrez Gene)
COX6A2GeneProduct1339 (Entrez Gene)
COX6B1GeneProduct1340 (Entrez Gene)
COX6B2GeneProduct125965 (Entrez Gene)
COX6CGeneProduct1345 (Entrez Gene)
COX7A1GeneProduct1346 (Entrez Gene)
COX7A2GeneProduct1347 (Entrez Gene)
COX7A2LGeneProduct9167 (Entrez Gene)
COX7BGeneProduct1349 (Entrez Gene)
COX7B2GeneProduct170712 (Entrez Gene)
COX7CGeneProduct1350 (Entrez Gene)
COX8AGeneProduct1351 (Entrez Gene)
COX8CGeneProduct341947 (Entrez Gene)
CXCL8GeneProduct3576 (Entrez Gene)
CYC1GeneProduct1537 (Entrez Gene)
CYCSGeneProduct54205 (Entrez Gene)
CYP2E1GeneProduct1571 (Entrez Gene)
CYTBGeneProduct4519 (Entrez Gene)
CxIGeneProduct
CxIIGeneProduct
CxIIIGeneProduct
CxIVGeneProduct
D-glucoseMetaboliteCHEBI:42758 (ChEBI)
DDIT3GeneProduct1649 (Entrez Gene)
EIF2AK3GeneProduct9451 (Entrez Gene)
EIF2S1GeneProduct1965 (Entrez Gene)
ERN1GeneProduct2081 (Entrez Gene)
FASGeneProduct355 (Entrez Gene)
FASLGGeneProduct356 (Entrez Gene)
FXRGeneProduct9971 (Entrez Gene)
Fatty Acid BiosynthesisPathwayWP357 (WikiPathways)
GSK3AGeneProduct2931 (Entrez Gene)
GSK3BGeneProduct2932 (Entrez Gene)
IKBKBGeneProduct3551 (Entrez Gene)
IL1AGeneProduct3552 (Entrez Gene)
IL1BGeneProduct3553 (Entrez Gene)
IL6GeneProduct3569 (Entrez Gene)
IL6RGeneProduct3570 (Entrez Gene)
INSGeneProduct3630 (Entrez Gene)
INSRGeneProduct3643 (Entrez Gene)
IRS1GeneProduct3667 (Entrez Gene)
IRS2GeneProduct8660 (Entrez Gene)
ITCHGeneProduct83737 (Entrez Gene)
Insulin SignalingPathwayWP481 (WikiPathways)
JNK1GeneProduct5599 (Entrez Gene)
JNK2GeneProduct5601 (Entrez Gene)
JUNGeneProduct3725 (Entrez Gene)
LEPGeneProduct3952 (Entrez Gene)
LEPRGeneProduct3953 (Entrez Gene)
Lipogenic EnzymesGeneProduct
MAP3K11GeneProduct4296 (Entrez Gene)
MAP3K5GeneProduct4217 (Entrez Gene)
MLXGeneProduct6945 (Entrez Gene)
MLXIPGeneProduct22877 (Entrez Gene)
MLXIPLGeneProduct51085 (Entrez Gene)
NDUFA10GeneProduct4705 (Entrez Gene)
NDUFA11GeneProduct126328 (Entrez Gene)
NDUFA12GeneProduct55967 (Entrez Gene)
NDUFA13GeneProduct51079 (Entrez Gene)
NDUFA1GeneProduct4694 (Entrez Gene)
NDUFA2GeneProduct4695 (Entrez Gene)
NDUFA3GeneProduct4696 (Entrez Gene)
NDUFA4GeneProduct4697 (Entrez Gene)
NDUFA4L2GeneProduct56901 (Entrez Gene)
NDUFA5GeneProduct4698 (Entrez Gene)
NDUFA6GeneProduct4700 (Entrez Gene)
NDUFA7GeneProduct4701 (Entrez Gene)
NDUFA8GeneProduct4702 (Entrez Gene)
NDUFA9GeneProduct4704 (Entrez Gene)
NDUFAB1GeneProduct4706 (Entrez Gene)
NDUFB10GeneProduct4716 (Entrez Gene)
NDUFB11GeneProduct54539 (Entrez Gene)
NDUFB1GeneProduct4707 (Entrez Gene)
NDUFB2GeneProduct4708 (Entrez Gene)
NDUFB3GeneProduct4709 (Entrez Gene)
NDUFB4GeneProduct4710 (Entrez Gene)
NDUFB5GeneProduct4711 (Entrez Gene)
NDUFB6GeneProduct4712 (Entrez Gene)
NDUFB7GeneProduct4713 (Entrez Gene)
NDUFB8GeneProduct4714 (Entrez Gene)
NDUFB9GeneProduct4715 (Entrez Gene)
NDUFC1GeneProduct4717 (Entrez Gene)
NDUFC2-KCTD14GeneProduct100532726 (Entrez Gene)
NDUFC2GeneProduct4718 (Entrez Gene)
NDUFS1GeneProduct4719 (Entrez Gene)
NDUFS2GeneProduct4720 (Entrez Gene)
NDUFS3GeneProduct4722 (Entrez Gene)
NDUFS4GeneProduct4724 (Entrez Gene)
NDUFS5GeneProduct4725 (Entrez Gene)
NDUFS6GeneProduct4726 (Entrez Gene)
NDUFS7GeneProduct374291 (Entrez Gene)
NDUFS8GeneProduct4728 (Entrez Gene)
NDUFV1GeneProduct4723 (Entrez Gene)
NDUFV2GeneProduct4729 (Entrez Gene)
NDUFV3GeneProduct4731 (Entrez Gene)
NFKB1GeneProduct4790 (Entrez Gene)
NR1H3GeneProduct10062 (Entrez Gene)
Oxidative PhosphorylationPathwayWP623 (WikiPathways)
PI3K-AKT SignalingPathwayWP3844 (WikiPathways)
PIK3CAGeneProduct5290 (Entrez Gene)
PIK3CBGeneProduct5291 (Entrez Gene)
PIK3CDGeneProduct5293 (Entrez Gene)
PIK3R1GeneProduct5295 (Entrez Gene)
PIK3R2GeneProduct5296 (Entrez Gene)
PIK3R3GeneProduct8503 (Entrez Gene)
PKLRGeneProduct5313 (Entrez Gene)
PPAR SignalingPathwayWP3942 (WikiPathways)
PPARAGeneProduct5465 (Entrez Gene)
PRKAA1GeneProduct5562 (Entrez Gene)
PRKAA2GeneProduct5563 (Entrez Gene)
PRKAB1GeneProduct5564 (Entrez Gene)
PRKAB2GeneProduct5565 (Entrez Gene)
PRKAG1GeneProduct5571 (Entrez Gene)
PRKAG2GeneProduct51422 (Entrez Gene)
PRKAG3GeneProduct53632 (Entrez Gene)
RAC1GeneProduct5879 (Entrez Gene)
RELAGeneProduct5970 (Entrez Gene)
ROSMetaboliteCHEBI:26523 (ChEBI)
RXRAGeneProduct6256 (Entrez Gene)
SDHAGeneProduct6389 (Entrez Gene)
SDHBGeneProduct6390 (Entrez Gene)
SDHCGeneProduct6391 (Entrez Gene)
SDHDGeneProduct6392 (Entrez Gene)
SMAD7GeneProduct4092 (Entrez Gene)
SOCS3GeneProduct9021 (Entrez Gene)
SREBF1GeneProduct6720 (Entrez Gene)
TCA CyclePathwayWP78 (WikiPathways)
TGF SignalingPathwayWP560 (WikiPathways)
TGFB1GeneProduct7040 (Entrez Gene)
TNF SignalingPathwayWP231 (WikiPathways)
TNFGeneProduct7124 (Entrez Gene)
TNFR1GeneProduct7132 (Entrez Gene)
TRAF2GeneProduct7186 (Entrez Gene)
UQCR10GeneProduct29796 (Entrez Gene)
UQCR11GeneProduct10975 (Entrez Gene)
UQCRBGeneProduct7381 (Entrez Gene)
UQCRC1GeneProduct7384 (Entrez Gene)
UQCRC2GeneProduct7385 (Entrez Gene)
UQCRFS1GeneProduct7386 (Entrez Gene)
UQCRHGeneProduct7388 (Entrez Gene)
UQCRHLGeneProduct440567 (Entrez Gene)
UQCRQGeneProduct27089 (Entrez Gene)
VCAM1GeneProduct7412 (Entrez Gene)
XBP1GeneProduct7494 (Entrez Gene)
fatty acidsMetaboliteCHEBI:35366 (ChEBI)
mir21Rna406991 (Entrez Gene)
oxysterolsMetaboliteCHEBI:53030 (ChEBI)
selonsertibMetaboliteQ27088777 (Wikidata)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP4396"
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